Obesity, diabetes and heart disease are characterized by resistance to insulin as a glucoregulatory hormone. African Americans, particularly African American women, suffer disproportionately from these conditions. We believe that African American women may have increased sensitivity to insulin?s ability to suppress lipolysis and this contributes to their accelerated development of obesity and related complications. The hypothesis of this research is that African American men are resistant to insulin as a glucoregulatory hormone and resistant to insulin as a fat regulatory hormone. In contrast, African American women are resistant to insulin as a glucoregulatory hormone but sensitive to insulin as a fat regulatory hormone. The frequently sampled intravenous glucose tolerance test is used to measure insulin?s action as a glucoregulatory hormone. Unfortunately there is no index of insulin?s action as a fat regulatory hormone. Hence we are working on the development of this index by obtaining free fatty acids during the frequently sampled glucose tolerance test. Our goal is be able to do one test to obtain information about both actions of insulin. However, the development of an index of free fatty acid sensitivity to insulin during the frequently sampled intravenous glucose tolerance test involves sophisticated mathematical modeling and will need to be validated. As we work towards developing this index, we have studied sex differences in triglyceride (TG) levels as well as body fat content and distribution in African Americans. We have found that TG levels are lower in African Americans than what is reported for Caucasians. Further TG levels are lower in African American women than men. One reason for this sex difference could be sex differences in body fat distribution. We determined using serial slice computerized tomographic scans from the iliac crest to the dome of the diaphragm that African American women have lower visceral fat volumes than men. As visceral fat is a major source of free fatty acids used to synthesize TG, this could be one reason for sex differences in TG levels. We also found that the activity of lipoprotein lipase (LPL), the enzyme responsible for clearing TG from the circulation, is not impaired in the presence of insulin resistance. Therefore even in the presence of insulin resistance African Americans are able to effectively clear TG from the circulation. While there was no sex difference in either the level of LPL activity or the effect of insulin resistance, the inability of insulin resistance to compromise LPL activity may contribute to why African Americans have lower TG levels than Caucasians. This is because in Caucasians, insulin resistance leads to a clear impairment of LPL activity and higher TG levels. Further, the lack of an effect on LPL activity may explain our additional finding, that unlike in Caucasians, TG levels cannot be used a marker of insulin resistance in African Americans.
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